A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing-Reference-Cited by-同舟云学术

A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing

Published:2020-03-22 Issue: Volume: Page:
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Gordon David E.,Jang Gwendolyn M.^ORCID,Bouhaddou Mehdi^ORCID,Xu Jiewei^ORCID,Obernier Kirsten^ORCID,O’Meara Matthew J.^ORCID,Guo Jeffrey Z.,Swaney Danielle L.^ORCID,Tummino Tia A.^ORCID,Hüttenhain Ruth^ORCID,Kaake Robyn M.^ORCID,Richards Alicia L.^ORCID,Tutuncuoglu Beril^ORCID,Foussard Helene,Batra Jyoti^ORCID,Haas Kelsey^ORCID,Modak Maya^ORCID,Kim Minkyu^ORCID,Haas Paige^ORCID,Polacco Benjamin J.^ORCID,Braberg Hannes^ORCID,Fabius Jacqueline M.,Eckhardt Manon^ORCID,Soucheray Margaret^ORCID,Bennett Melanie J.,Cakir Merve^ORCID,McGregor Michael J^ORCID,Li Qiongyu^ORCID,Naing Zun Zar Chi^ORCID,Zhou Yuan^ORCID,Peng Shiming,Kirby Ilsa T.^ORCID,Melnyk James E.^ORCID,Chorba John S.^ORCID,Lou Kevin^ORCID,Dai Shizhong A.^ORCID,Shen Wenqi^ORCID,Shi Ying^ORCID,Zhang Ziyang^ORCID,Barrio-Hernandez Inigo^ORCID,Memon Danish^ORCID,Hernandez-Armenta Claudia^ORCID,Mathy Christopher J.P.^ORCID,Perica Tina^ORCID,Pilla Kala B.^ORCID,Ganesan Sai J.^ORCID,Saltzberg Daniel J.^ORCID,Ramachandran Rakesh^ORCID,Liu Xi,Rosenthal Sara B.^ORCID,Calviello Lorenzo^ORCID,Venkataramanan Srivats^ORCID,Lin Yizhu^ORCID,Wankowicz Stephanie A.^ORCID,Bohn Markus^ORCID,Trenker Raphael^ORCID,Young Janet M.^ORCID,Cavero Devin^ORCID,Hiatt Joe^ORCID,Roth Theo^ORCID,Rathore Ujjwal^ORCID,Subramanian Advait^ORCID,Noack Julia,Hubert Mathieu,Roesch Ferdinand,Vallet Thomas,Meyer Björn,White Kris M.^ORCID,Miorin Lisa^ORCID,Agard David^ORCID,Emerman Michael^ORCID,Ruggero Davide^ORCID,García-Sastre Adolfo^ORCID,Jura Natalia^ORCID,Zastrow Mark von^ORCID,Taunton Jack^ORCID,Schwartz Olivier^ORCID,Vignuzzi Marco^ORCID,d’Enfert Christophe^ORCID,Mukherjee Shaeri^ORCID,Jacobson Matt,Malik Harmit S.^ORCID,Fujimori Danica G.^ORCID,Ideker Trey^ORCID,Craik Charles S.^ORCID,Floor Stephen^ORCID,Fraser James S.^ORCID,Gross John^ORCID,Sali Andrej^ORCID,Kortemme Tanja^ORCID,Beltrao Pedro^ORCID,Shokat Kevan^ORCID,Shoichet Brian K.^ORCID,Krogan Nevan J.^ORCID

Abstract

ABSTRACTAn outbreak of the novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 290,000 people since the end of 2019, killed over 12,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven efficacy nor are there vaccines for its prevention. Unfortunately, the scientific community has little knowledge of the molecular details of SARS-CoV-2 infection. To illuminate this, we cloned, tagged and expressed 26 of the 29 viral proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), which identified 332 high confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 existing FDA-approved drugs, drugs in clinical trials and/or preclinical compounds, that we are currently evaluating for efficacy in live SARS-CoV-2 infection assays. The identification of host dependency factors mediating virus infection may provide key insights into effective molecular targets for developing broadly acting antiviral therapeutics against SARS-CoV-2 and other deadly coronavirus strains.

Publisher

Cold Spring Harbor Laboratory

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